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Driver mutations lung cancer

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https://www.readbyqxmd.com/read/29221323/management-of-non-small-cell-lung-cancer-with-egfr-mutation-the-role-of-radiotherapy-in-the-era-of-tyrosine-kinase-inhibitor-therapy-opportunities-and-challenges
#1
REVIEW
Bing Xia, Shirong Zhang, Shenglin Ma
In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) was greatly promoted by the discovery of oncogenic drivers and the development of targeted therapies specific for these drivers. Somatic mutations in epidermal growth factor receptor (EGFR) are the most common type in patients with NSCLC. Small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR produced relatively high response rate and long duration with acceptable toxicity profile. Also, the life expectancy in patients with active EGFR mutation has been significantly prolonged than the past...
September 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29217530/the-impact-of-smoking-and-tp53-mutations-in-lung-adenocarcinoma-patients-with-targetable-mutations-the-lung-cancer-mutation-consortium-lcmc2
#2
Dara L Aisner, Lynette M Sholl, Lynne Berry, Michael Rossi, Heidi Chen, Junya Fujimoto, Andre L Moreira, Suresh Ramalingam, Liza C Villaruz, Gregory A Otterson, Eric B Haura, Katerina Politi, Bonnie S Glisson, Jeremy Cetnar, Edward Garon, Joan Schiller, Saiama Waqar, Lecia V Sequist, Julie R Brahmer, Yu Shyr, Kelly Kugler, Ignacio Ivan Wistuba, Bruce E Johnson, John D Minna, Mark G Kris, Paul A Bunn, David J Kwiatkowski
PURPOSE Multiplex genomic profiling is standard of care for patients with advanced lung adenocarcinomas. The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional effort to identify and treat oncogenic driver events in patients with lung adenocarcinomas. PATIENTS AND METHODS Sixteen U.S. institutions enrolled 1367 lung cancer patients in LCMC2; 904 were deemed eligible and had at least one of 14 cancer-related genes profiled using validated methods including genotyping, massively parallel sequencing, and immunohistochemistry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29215816/efficacy-of-afatinib-in-a-previously-treated-patient-with-non-small-cell-lung-cancer-harboring-her2-mutation-case-report
#3
Cheol Kyu Park, Jae Young Hur, Chang Min Choi, Tae Ok Kim, Hyun Ju Cho, Hong Joon Shin, Jung Hwan Lim, Yoo Duk Choi, Young Chul Kim, In Jae Oh
Human epidermal growth factor receptor 2 (HER2) mutation in non-small cell lung cancer (NSCLC) is an oncogenic driver that possibly becomes a druggable target to HER2-targeted therapy. The benefit of HER2-targeted therapy is much less defined especially in eastern populations. We provide evidence of clinical benefit of afatinib in a 50-year-old Asian woman with HER2-mutant NSCLC who previously failed cytotoxic chemotherapy and gefitinib treatment. Next-generation sequencing of the tumor tissue revealed a HER2 exon 20 mutation (c...
January 1, 2018: Journal of Korean Medical Science
https://www.readbyqxmd.com/read/29213088/nsd1-inactivation-defines-an-immune-cold-dna-hypomethylated-subtype-in-squamous-cell-carcinoma
#4
Kevin Brennan, June Ho Shin, Joshua K Tay, Marcos Prunello, Andrew J Gentles, John B Sunwoo, Olivier Gevaert
Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211692/a-molecular-and-cytogenetic-update-on-non-small-cell-lung-carcinoma
#5
Maximilian Becker, Lori Ryan, Alexis Dowiak, Carlos A Tirado
Lung cancer is one of the leading causes of cancer-related death worldwide. Among patients with lung cancer, approximately 85% have non-small cell lung carcinoma (NSCLC). The discovery of oncogenic driver mutations in NSCLC opened new personalized treatment options. Several methods that can identify these biomarkers are used routinely in a clinical setting to stratify patients for targeted therapy. In this review, we summarize the most clinically relevant driver genes, discuss the advantages and limitations of current clinical detection methods, and highlight the benefits of personalized treatment over standard chemotherapy...
2017: Journal of the Association of Genetic Technologists
https://www.readbyqxmd.com/read/29199686/first-line-therapy-outcomes-in-patients-with-advanced-stage-nonsmall-cell-lung-cancer-treated-at-nongovernment-tertiary-care-centrer-in-india-experience-from-a-real-world-practice
#6
S S Hingmire, M B Sambhus, D S Kelkar, S W Joshi, K S Narsinghpura
INTRODUCTION: Reports on first line or subsequent treatment and their outcomes for patients with advanced nonsmall cell lung cancer (NSCLC) in India are scarce. The present study is an attempt to understand real world practice scenario of first-line therapy and outcome in advanced stage NSCLC patients. METHODS: Observational study was conducted at a nongovernment tertiary cancer care center. Totally 83 patients with newly diagnosed advanced NSCLC who were evaluated for further treatment from 2008 onward were included in the study...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29199685/role-of-crizotinib-in-c-mesenchymal-epidermal-transition-positive-nonsmall-cell-lung-cancer-patients
#7
U Batra, A Jain, M Sharma, R Bajaj, M Suryavanshis
The increasing cases of NSCLC and improved understanding of its molecular biology has lead to identification of its varied driver mutations. cMET amplification has an important role as resistance mechanism for EGFR TKIs. Crizotinib is a drug which shows its anti-tumoral effect in cMET positive cases. Here we present a case series of three such patients who achieved were cMET amplified and showed partial response on Crizotinib.
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29199671/indian-consensus-statement-for-treatment-of-advanced-non-small-cell-lung-cancer-first-line-maintenance-and-second-line
#8
REVIEW
(no author information available yet)
The management of advanced nonsmall cell lung cancer (NSCLC) patients is becoming complex with the identification of driver mutations and targeted therapies. The expert group of academic medical oncologists used data from published literature, practical experience to arrive at practical consensus recommendations to treat advanced NSCLC for use by the community oncologists.
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29198084/-the-impact-of-molecular-profiling-using-next-generation-sequencing-in-advanced-lung-cancer
#9
Anna Belilovski Rozenblum, Maya Ilouze, Elizabeth Dudnik, Lior Soussan-Gutman, Addie Dvir, Nir Peled
BACKGROUND: In the last decade, important advances in understanding the lung cancer cellular signal pathways have led to the designing of targeted drugs that significantly prolong survival. Recent data shows that 64% of lung adenocarcinomas harbor at least one activating driver mutation, including treatable mutations such as RET, ERBB2 (HER-2) and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes. Next-Generation Sequencing (NGS) reveals more clinically meaningful genomic alterations as compared to currently used diagnostic tests...
November 2017: Harefuah
https://www.readbyqxmd.com/read/29197663/prediction-of-potential-drivers-connecting-different-dysfunctional-levels-in-lung-adenocarcinoma-via-a-protein-protein-interaction-network
#10
Fei Yuan, WenCong Lu
Lung cancer is a serious disease that threatens an affected individual's life. Its pathogenesis has not yet to be fully described, thereby impeding the development of effective treatments and preventive measures. "Cancer driver" theory considers that tumor initiation can be associated with a number of specific mutations in genes called cancer driver genes. Four omics levels, namely, (1) methylation, (2) microRNA, (3) mutation, and (4) mRNA levels, are utilized to cluster cancer driver genes. In this study, the known dysfunctional genes of these four levels were used to identify novel driver genes of lung adenocarcinoma, a subtype of lung cancer...
November 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29196555/ral-gtpases-biology-and-potential-as-therapeutic-targets-in-cancer
#11
REVIEW
Chao Yan, Dan Theodorescu
More than a hundred proteins comprise the RAS superfamily of small GTPases. This family can be divided into RAS, RHO, RAB, RAN, ARF, and RAD subfamilies, with each shown to play distinct roles in human cells in both health and disease. The RAS subfamily has a well-established role in human cancer with the three genes, HRAS, KRAS, and NRAS being the commonly mutated in tumors. These RAS mutations, most often functionally activating, are especially common in pancreatic, lung, and colorectal cancers. Efforts to inhibit RAS and related GTPases have produced inhibitors targeting the downstream effectors of RAS signaling, including inhibitors of the RAF-mitogen-activated protein kinase/extracellular signal-related kinase (ERK)-ERK kinase pathway and the phosphoinositide-3-kinase-AKT-mTOR kinase pathway...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29188469/met-targeting-antibody-emibetuzumab-and-kinase-inhibitor-merestinib-as-single-agent-or-in-combination-in-a-cancer-model-bearing-met-exon-14-skipping
#12
S Betty Yan, Suzane L Um, Victoria L Peek, Jennifer R Stephens, Wei Zeng, Bruce W Konicek, Ling Liu, Jason R Manro, Volker Wacheck, Richard A Walgren
Purpose Approximately 3% of lung cancer bears mutations leading to MET exon 14 skipping, an oncogenic driver which is further evidenced by case reports of patient response to MET kinase inhibitor treatment. Approximately 15% of tumors harboring MET exon14 skipping have concurrent MET amplification. Experimental Design Merestinib is a type II MET kinase inhibitor. Emibetuzumab, a bivalent anti-MET antibody, internalizes MET receptor. Each single agent and the combination were evaluated in the Hs746t gastric cancer line bearing MET exon14 skipping and MET amplification...
November 29, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29186353/prevalence-and-clinical-association-of-gene-mutations-through-multiplex-mutation-testing-in-patients-with-nsclc-results-from-the-etop-lungscape-project
#13
K M Kerr, U Dafni, K Schulze, E Thunnissen, L Bubendorf, H Hager, S Finn, W Biernat, L Vliegen, J H Losa, A Marchetti, R Cheney, A Warth, E-J Speel, F Blackhall, K Monkhorst, E Jantus Lewintre, V Tischler, C Clark, J Bertran-Alamillo, P Meldgaard, K Gately, A Wrona, P Vandenberghe, E Felip, G De Luca, S Savic, T Muley, E F Smit, A-M C Dingemans, L Priest, P Baas, C Camps, W Weder, V Polydoropoulou, T R Geiger, R Kammler, T Sumiyoshi, M A Molina, D S Shames, R A Stahel, S Peters
Background: Reported prevalence of driver gene mutations in non-small cell lung cancer (NSCLC) is highly variable and clinical correlations are emerging. Using NSCLC biomaterial and clinical data from the ETOP Lungscape iBiobank, we explore the epidemiology of mutations and association to clinicopathological features and patient outcome (relapse-free survival, time-to-relapse, overall survival). Methods: Clinically-annotated, resected stage I-III NSCLC FFPE tissue was assessed for gene mutation using a microfluidics-based multiplex PCR platform...
November 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29184501/identification-of-a-new-potent-inhibitor-targeting-kras-in-non-small-cell-lung-cancer-cells
#14
Chun Xie, Ying Li, Lan-Lan Li, Xing-Xing Fan, Yu-Wei Wang, Chun-Li Wei, Liang Liu, Elaine Lai-Han Leung, Xiao-Jun Yao
KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is an oncogenic driver with mutations in 30% of non-small cell lung cancer (NSCLC). However, there is no effective clinical drug even though it has been identified as an oncogene for 30 years. In this study, we identified a small molecule inhibitor compound 0375-0604 targeting KRAS by using molecular docking based virtual screening approach. Compound 0375-0604 had a good binding affinity to KRAS in vitro and exhibited cytotoxicity in oncogenic KRAS expressing NSCLC cell lines...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29183778/current-who-guidelines-and-the-critical-role-of-immunohistochemical-markers-in-the-subclassification-of-non-small-cell-lung-carcinoma-nsclc-moving-from-targeted-therapy-to-immunotherapy
#15
REVIEW
Lais Osmani, Frederic Askin, Edward Gabrielson, Qing Kay Li
Recent large scale genomic studies from the Clinical Lung Cancer Genome Project have identified different driver gene mutations in the subtypes of non-small cell lung carcinoma (NSCLC). These findings not only lead to remarkable progress in targeted therapies for lung cancer patients, but also provide fundamental knowledge for the subclassification of NSCLC. More recently, the advancement and clinical application of immunotherapy have reinforced the need for the accurate subclassification of NSCLC. In 2015, the World Health Organization (WHO) and the International Association for the Study of Lung Cancer (IASLC) updated their guidelines for the subclassification of lung cancers...
November 25, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29180607/small-cell-carcinomas-of-the-bladder-and-lung-are-characterized-by-a-convergent-but-distinct-pathogenesis
#16
Matthew T Chang, Alexander V Penson, Neil B Desai, Nicholas D Socci, Ronglai Shen, Venkatraman Seshan, Ritika Kundra, Adam A Abeshouse, Agnes Viale, Eugene K Cha, Xueli Hao, Victor Reuter, Charles M Rudin, Bernard H Bochner, Jonathan E Rosenberg, Dean F Bajorin, Nikolaus Schultz, Michael F Berger, Gopa Iyer, David B Solit, Hikmat A Al-Ahmadie, Barry S Taylor
Background Small cell carcinoma of the bladder (SCCB) is a rare and aggressive neuroendocrine tumor with a dismal prognosis and limited treatment options. As SCCB is histologically indistinguishable from small cell lung cancer, a shared pathogenesis and cell of origin has been proposed. The aim of this study is to determine whether SCCBs arise from a pre-existent urothelial carcinoma or share a molecular pathogenesis in common with small cell lung cancer. Results We performed an integrative analysis of 61 SCCB tumors to identify histology- and organ-specific similarities and differences...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29167009/-advances-of-the-role-of-lung-cancer-driver-gene-and-pd-1-pd-l1-pathway-interaction-in-the-tumorigenesis-and-progression-of-non-small-cell-lung-cancer
#17
Yan Shi, Wang Lv, Luming Wang, Jian Hu
Programmed death 1 (PD-1) and programmed death 1 ligand (PD-L1) pathway is a key mechanism of immune regulation, and its abnormal activation in tumor tissues suggests that PD-1/PD-L1 pathway may participate in the regulation of tumor immune escape. Driver gene mutation which is known as a key factor in the tumorigenesis of non-small cell lung cancer (NSCLC), was also reported to play a important role in the process of tumor immune escape. It indicates that there is an interaction between driver gene and PD-1/PD-L1 pathway...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29167003/-prognostic-analysis-of-patients-with-advanced-non-small-cell-lung-cancer-%C3%A2-in-different-genotypes
#18
Ping Liu, Yuhua Wu, Lijuan Zhou, Na Qin, Quan Zhang, Hui Zhang, Xi Li, Xinyong Zhang, Jialin Lv, Xinjie Yang, Jinghui Wang, Shucai Zhang
BACKGROUND: Non-small cell lung cancer (NSCLC) has been transformed from the treatment according to histological type to genotype treatment model. The epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes are the most important drivers in lung cancer. The aim of this study is to explore the clinical characteristics and prognostic factors of patients with advanced NSCLC with different genotypes. METHODS: We retrospectively reviewed the clinical data of 553 advanced NSCLC patients with EGFR mutations and ALK positive who were hospitalized in the Beijing Chest Hospital from July 2004 to December 2015, and the independent prognostic factors of patients were analyzed by Cox proportional hazards regression model...
November 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29153898/the-significance-of-the-pd-l1-expression-in-non-small-cell-lung-cancer-trenchant-double-swords-as-predictive-and-prognostic-markers
#19
REVIEW
Kazuki Takada, Gouji Toyokawa, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Lung cancer is the leading cause of death due to cancer worldwide. Surgery, chemotherapy, and radiotherapy have been the standard treatment for lung cancer, and targeted molecular therapy has greatly improved the clinical course of patients with non-small-cell lung cancer (NSCLC) harboring driver mutations, such as in epidermal growth factor receptor and anaplastic lymphoma kinase genes. Despite advances in such therapies, the prognosis of patients with NSCLC without driver oncogene mutations remains poor. Immunotherapy targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) has recently been shown to improve the survival in advanced NSCLC...
October 28, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29152593/resistance-is-futile-overcoming-resistance-to-targeted-therapies-in-lung-adenocarcinoma
#20
Dana S Neel, Trever G Bivona
The advent of genomics has led to the identification of specific "driver" mutations in oncogenic kinases, and the development of targeted small molecule inhibitors to block their tumor-driving functions. These specific inhibitors have been a clinical success, and often significantly prolong the lives of individuals with cancer. Inevitably, however, the treated tumors recur as resistance to these targeted therapies develops. Here, we review the major mechanisms by which a cancer cell can evade targeted therapy, focusing on mechanisms of resistance to kinase inhibitors in lung cancer...
2017: NPJ Precision Oncology
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